PATH receives new funding to study meningococcal and rotavirus vaccines

PATH’s vaccine development program recently received a grant for £3,619,788 from the United Kingdom’s Department for International Development to develop an affordable thermostable pentavalent conjugate meningococcal vaccine through a Phase 1 clinical trial, over a period of five years. Building on the work by PATH’s Meningitis Vaccine Project in developing the MenAfriVac™ conjugate vaccine against group A meningococcal disease, this new vaccine will cover five serotype groups: A, C, W, Y, and X. The goal is a vaccine that would have a four-year shelf life at room temperature and be stable for 30 days at 45°C, making it highly suitable for use in Africa during meningitis epidemics. This would reduce vaccine cold-chain storage requirements and dramatically simplify vaccine-stock management, making it cost-effective to maintain meningococcal vaccine stocks in African sites where the vaccines could be mobilized far more expeditiously than is now possible.

In addition, PATH received a separate grant for US$4,999,724 from the Bill & Melinda Gates Foundation to conduct targeted immunogenicity studies and analyses over a period of four years to better understand the performance of rotavirus vaccines among children in developing countries. The project will study two commercial rotavirus vaccines manufactured by GlaxoSmithKline and Merck & Co, Inc., in an attempt to elucidate reasons for the varying efficacies between children living in developed countries and those living in impoverished countries and to identify strategies for improving efficacy in those countries with the highest disease burden. The research questions that form the basis for these new clinical studies were identified by a consortium that includes PATH, the US Centers for Disease Control and Prevention, and Johns Hopkins University, as well as the project’s international partner institutions including Aga Khan University, University of the Witwatersrand, the International Vaccine Institute, and the Norwegian Institute of Public Health. 

Clinical trial underway to advance pneumococcal protein vaccines

PATH and its pneumococcal vaccine project partners—GlaxoSmithKline Biologicals SA, the Medical Research Council The Gambia, and the London School of Hygiene and Tropical Medicine—recently launched a two-stage Phase 2 clinical trial of an innovative vaccine candidate against Streptococcus pneumoniae in Fajikunda, The Gambia. The vaccine candidate includes an innovative combination of protein and conjugate vaccine technologies designed to provide protection against a broader range of pneumococcal diseases than the existing licensed vaccines. The first stage of the trial began in February to evaluate the vaccine candidate’s tolerability and immunogenicity in Gambian children. In this part of the study, 120 children two to four years of age were enrolled and received either the vaccine candidate or a control pneumococcal vaccine, Prevnar 13®. Pending satisfactory data from this stage, the study will move into its second part to evaluate the vaccine candidate’s tolerability, immunogenicity, and impact on nasopharyngeal carriage in Gambian infants eight to ten weeks of age. Overall, trial results could shed light on the potential of protein-based approaches to generate more protective pneumococcal vaccines for young children hardest hit by pneumococcal disease, a large proportion of whom are in Africa. The initiation of this trial followed an epidemiological study of nasopharyngeal carriage of S. pneumoniae and other bacteria among infants in The Gambia.

New market assessment report and trial launched for vaccines against leading bacterial causes of diarrhea

PATH partnered with BIO Ventures for Global Health to publish a new report entitled, The Case for Investment in Enterotoxigenic Escherichia coli Vaccines. The report aims to increase the awareness of biotechnology and pharmaceutical companies worldwide about the opportunities and potential markets that exist for low-cost and effective vaccines against enterotoxigenic Escherichia coli (ETEC). In addition, it provides donors and commercial investors with a better understanding of the potential risks, rewards, and gaps in knowledge relative to these opportunities as they consider their own investment strategies. The resulting analysis demonstrates that ETEC vaccines may represent a moderate opportunity for industry investment, with an estimated annual revenue potential of more than US$600 million 10 years after global launch.

In related news, PATH’s enteric vaccine project supported the launch of a Phase 1 trial of an oral Shigella vaccine candidate in March. The trial is taking place in Baltimore, Maryland, at Johns Hopkins University in partnership with the EMMES Corporation and will test the safety and immunogenicity of an inactivated whole cell Shigella flexneri 2a vaccine candidate. Researchers are administering up to three vaccine doses to nearly 60 healthy adults participating in the study, which is testing three different dose levels. The trial is expected to conclude by the end of 2011 with results available by March 2012.

PATH organizes training session on liquid formulation for rotavirus vaccine candidates

PATH’s rotavirus vaccine development project has developed a training session on the preparation of a liquid formulation developed by Aridis Pharmaceuticals and PATH for the “shared technology platform” partners that have licensed the bovine-human reassortant vaccine (BRV). PATH supports the emerging-country manufacturers actively developing BRV candidates by giving them access to a host of technologies, training, methodologies, and material through this platform. As part of this effort, PATH collaborated with Aridis to identify two liquid formulations with satisfactory stability. A team from PATH’s Technology Solutions Global Program then performed additional studies on the two formulations to address viscosity, precipitation, solubilization, and buffering capacity, as well as to improve the blending procedure developed by Aridis. This work resulted in an optimized liquid formulation that the manufacturers may now choose to use with their BRV candidates.

Two representatives from Serum Institute of India, Ltd., participated in the first training session at PATH’s headquarters in Seattle, Washington, on April 4 to 12. The session included a review of the blending protocol, preparation of reagents, preparation of the formulation, scale-up, stability testing, and formulation troubleshooting. PATH hopes to plan more training sessions in the future for other manufacturing partners participating in the shared technology platform. 

Recent scientific publications

Several staff from PATH’s vaccine development program recently contributed to new scientific publications, including the following articles:

• Laboratory-based diagnosis of pneumococcal pneumonia: State of the art and unmet needs summarizes a meeting organized by PATH and Fondation Mérieux from October 18 to 20, 2009 in Les Pensiéres, France, during which participants evaluated current pneumococcal diagnostics and serotyping methodologies, identified research and development needs, and proposed new public-health guidelines to support pneumococcal vaccine introduction. Drs. Mark Alderson and Jean-Francois Maisonneuve were co-authors of this article published in Clinical Microbiology and Infection.
• New conjugate vaccines for the prevention of pneumococcal disease provides an overview of currently available pneumococcal conjugate vaccines (PCVs) and outlines several new approaches in the pipeline for PCVs designed to meet needs in the developing world. Drs. Amy Ginsburg and Mark Alderson authored this article, which appeared in Drugs of Today.
• T_H17-based vaccine design for prevention of Streptococcus pneumoniae colonization describes preclinical research conducted by Children’s Hospital Boston and Genocea Biosciences with support from PATH using a comprehensive proteomic screening approach to identify T cell antigens that could be strong candidates for protein subunit pneumococcal vaccines. Dr. Mark Alderson was a co-author of this article published in Cell Host & Microbe.

Also@PATH: Jet injector project achieves key milestone in clinical research

In addition to developing new vaccines, PATH also works on new technologies to improve vaccine delivery in developing-country populations. The Disposable-Syringe Jet Injector project recently met a major milestone by completing fieldwork for a vaccine study comparing disposable-syringe jet injectors (DSJIs or jet injectors) to traditional needle and syringe. According to the World Health Organization, at least 50 percent of injections given in developing countries are unsafe, putting people at risk of infection and spreading disease such as HIV and hepatitis. Jet injectors use pressure rather than needles to deliver vaccines and medicines through the skin and into the tissue. They improve injection safety by eliminating needle and syringe reuse, preventing needle-stick injuries, and reducing the overall burden of sharps waste.

For a number of years, PATH has worked with DSJI manufacturers and global stakeholders to advance the DSJI potential for developing-country use. In addition to conducting user assessments and recommending design adjustments based on user feedback, PATH has also worked to evaluate the cost effectiveness of DSJIs. PATH has now completed a key milestone toward demonstrating their clinical performance and acceptability among patients and health-care workers alike. PATH collaborated with a Brazilian vaccine manufacturer, Bio-Manguinhos Fiocruz, to immunize 600 infants in Rio de Janeiro, Brazil, with measles-mumps-rubella (MMR) vaccine. Infants were immunized either with a DSJI, or with a traditional needle and syringe. Preliminary analysis of study data reflects favorably on MMR vaccine delivery with a jet injector. The DSJI project looks forward to sharing more details as data becomes available.